Drug addiction is linked to behavioral sensitization in several animal models and humans. Changes in the expression levels of several genes have been shown to correlate with exposure to cocaine or other drugs of abuse in vertebrates. The fruit fly Drosophila melanogaster has been shown to sensitize to intermittent exposure to volatile free base ?crack? cocaine. To test the hypothesis that changes in gene expression are necessary and sufficient for sensitization, global changes in gene expression in the fly brain that occur during sensitization to cocaine will be analyzed by a microarray approach. Further, mutants will be identified for those genes whose levels of transcript correlate with sensitization, to test whether they are required for sensitization. Finally, overexpression of these genes will be tested for their effects on the expression of behavioral sensitization. The results of these studies should shed light on the molecular basis of sensitization to drugs of abuse. This information could lead to new pharmacological targets for treatment of drug addiction.